HMGN2 regulates non-tuberculous mycobacteria survival via modulation of M1 macrophage polarization.

Abstract

Non-tuberculous mycobacteria (NTM), also known as an environmental and atypical mycobacteria, can cause the chronic pulmonary infectious diseases. Macrophages have been suggested as the main host cell to initiate the innate immune responses to NTM infection. However, the molecular mechanism to regulate the antimicrobial immune responses to NTM is still largely unknown. Current study showed that the NTM clinical groups, Mycobacterium abscessus and Mycobacterium smegmatis, significantly induced the M1 macrophage polarization with the characteristic production of nitric oxide (NO) and marker gene expression of iNOS, IFNγ, TNF-α, IL1-β and IL-6. Interestingly, a non-histone nuclear protein, HMGN2 (high-mobility group N2), was found to be spontaneously induced during NTM-activated M1 macrophage polarization. Functional studies revealed that HMGN2 deficiency in NTM-infected macrophage promotes the expression of M1 markers and the production of NO via the enhanced activation of NF-κB and MAPK signalling. Further studies exhibited that HMGN2 knock-down also enhanced IFNγ-induced M1 macrophage polarization. Finally, we observed that silencing HMGN2 affected the survival of NTM in macrophage, which might largely relevant to enhanced macrophage polarization into M1 phenotype under the NTM infection. Collectively, current studies thus suggested a novel function of HMGN2 in regulating the anti-non-tuberculous mycobacteria innate immunity of macrophage.

• Authors: Xinyuan Wang, Shanze Chen, Hongyu Ren, Junli Chen, Jingyu Li, Yi Wang, Yuanqi Hua, Xiaoying Wang, Ning Huang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 12 Pg. 7985-7998 (12 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 31596045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• HMGN2 Protein
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Interferon-gamma
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse

Topics

• Animals
• Cell Survival (genetics)
• Gene Knockdown Techniques
• Gene Silencing
• HMGN2 Protein (genetics, metabolism)
• Humans
• Immunity, Innate
• Interferon-gamma (metabolism)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• MAP Kinase Signaling System (genetics)
• Macrophage Activation (genetics)
• Macrophages (metabolism)
• Mice
• Mycobacterium Infections (immunology)
• Mycobacterium abscessus (immunology, isolation & purification)
• Mycobacterium smegmatis (immunology, isolation & purification)
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Nontuberculous Mycobacteria (growth & development)
• RAW 264.7 Cells
• RNA Interference
• Tumor Necrosis Factor-alpha (metabolism)